1. Field of the Invention
The present invention relates to a method of preparing an optically pure phenethylamine derivative which is an intermediate useful for preparing tamsulosin or its salts and a method of preparing tamsulosin or its salts using the optically pure phenethylamine derivative.
2. Description of the Related Art
Tamsulosin or its salts (for example, hydrochloride) exhibit an action of blocking α-adrenaline and are known as therapeutic agents for benign prostatic hypertrophy, hypertension, and congestive heart failure. The chemical name of tamsulosin is (R)-5-{2-[2-(2-ethoxyphenoxy)ethylamino]-propyl}-2-methoxybenzenesulfonamide and has an asymmetric carbon as seen from the following chemical structure. Thus, there is a need to obtain said compound in an optically pure form, i.e., (R)-form.

U.S. Pat. Nos. 4,217,305 and 4,373,106 describe methods of preparing tamsulosin or its salts using racemic compounds, as shown in scheme 1. However, in these methods, the compounds in racemic forms are obtained by using achiral compounds as the starting materials, and thus, a single isomeric compound cannot be easily isolated from the obtained compounds. Especially, the single isomeric compound cannot be obtained in about 50% or more, thereby resulting low yield.

Korean Laid-Open Patent Publication No. 1994-7746 describes a method of preparing tamsulosin or its hydrochloride using a chiral amine, as shown in scheme 2. However, in the N-akylating reaction, which is a main reaction of the method, reactants are primary amines, and thus, a side reaction, such as alkylation, of the reactants, can occur. A sulfonamide group can also be subjected to alkylation, and thus, a side reaction can occur. Accordingly, the reaction yield is low and products of the side reactions should be separately removed.

Japanese Laid-Open Patent Publication Nos. Hei 2-295967 and 2-306958 describe methods of preparing tamsulosin and its hydrochloride. In the methods, 2-(4-methoxyphenyl)-1-methylethylamine, which does not have an aminosulfonyl group, as a starting material was reacted with bromoacetyl chloride, etc. in an N-alkylation reaction and an aminosulfonyl group was introduced into the resultant product to obtain an intermediate. Then, the intermediate was reacted with ethoxy phenol and reduced.

However, in this method, the compound which does not have an aminosulfonyl group should be used to prevent a side reaction occurring due to the use of highly reactive reactants, such as acid chloride, etc. Further, a further reaction process should be performed, i.e., the introduction of an aminosulfonyl group into the resultant product.
Thus, a method of preparing tamsulosin or its salts which can prevent a side reaction and formation of racemic compounds and increase an yield of production is required.